Intraluminal Pressure Modulates Vascular Contractility of Perfused Mesenteric Resistance Arteries: Altered Response in Hypertension

Intraluminal pressure may affect vascular contractility in both normotension and hypertension. To test this hypothesis, we studied mesenteric resistance arteries from normotensive humans as well as normotensive (WKY) and spontaneously hypertensive (SHR) rats (internal diameter 214 ± 27, 201 ± 6, and 172 ± 6 μm, mean ± SEM at 10 mm Hg). Vessels were mounted on glass cannulas and perfused in organ chambers filled with buffer solution at intraluminal pressures of 10 to 120 mm Hg; vasomotion was measured using a video dimension analyzer. Under baseline conditions (10 mm Hg), wall thickness was 36 ± 4 μm in humans, 32 ± 4 μm in WKY, and 47 ± 2 μm in SHR (P < .001). With increasing pressure, the diameter of human vessels increased up to 25 mm Hg and remained constant at higher pressures. In contrast, resistance arteries of normotensive and hypertensive rats exhibited an almost linear increase in diameter over the whole pressure range. In SHR, the pressure-diameter relationship was much flatter than that of WKY, indicating reduced compliance. In human arteries, the contraction to KCl was maximal at 25 mm Hg and averaged 40 ± 6%. Both above and below 25 mm Hg, the response declined to a minimum of 17 ± 2% at 120 mm Hg (P < .01). Similar results were obtained in WKY rats. In contrast, the contractile response in SHR remained maximal over the entire pressure range studied (65 ± 5%). Thus, intraluminal pressure profoundly affects vascular reactivity of resistance arteries; low pressure augments and high pressure reduces the contractile response in normotensive human and rat resistance arteries, whereas this pressure-dependent modulation of vascular reactivity is lost in the SHR. Am J Hypertens 1992;5:542-54

Angiotensin-Induced Growth Related Metabolism Is Activated in Cultured Smooth Muscle Cells From Spontaneously Hypertensive Rats and Wistar-Kyoto Rats

Smooth muscle cells from spontaneously hypertensive rats (SHR) proliferate in culture faster than those isolated from sex- and age-matched Wistar- Kyoto (WKY) animals. There was no difference in the kinetics of S6 kinase activation in the two cultures, but later metabolic events associated with proliferation were stimulated earlier in SHR cells than in WKY, eg, activation of ornithine decarboxylase. Both cell types elaborated an extensive extracellular matrix in culture composed of a different blend of connective tissue macromolecules. Matrix material from SHR cells was more stimulatory to growth of WKY cultures than their own matrices. Angiotensin stimulated the growth and synthesis of extra-cellular matrix material in SHR more than in WKY derived vascular smooth muscle cell cul-tures. Am J Hypertens 1991;4:183-18

Atrial Natriuretic Peptide: Binding and Cyclic GMP Response in Cultured Vascular SmoothMuscle Cells From Spontaneously Hypertensive Rats

Atrial natriuretic peptide (ANP) is vasodilatory and natriuretic, but whereas increased plasma ANP levels occur in spontaneously hypertensive rats, their elevated vascular resistance suggests inappropriate target tissue responsiveness to ANP. This study examines ANP-receptor binding properties (at 25 °C and 4°C) in cultured vascular aortic smooth muscle cells from spontaneously hypertensive (SHR) and control Wistar-Kyoto (WKY) rats. [I125]-human ANP saturation (0.0625-12.0 nmol) profiles were analyzed using nonlinear regression (LIGAND). Vascular smooth muscle cells from WKY possessed both high affinity (KD1 0.3 nmol; R1 33 fmol/105 cells) and low affinity (KD2 15 nmol; R2 400 fmol/105 cells) binding sites for ANP. In contrast, for smooth muscle cells from SHR, two receptor forms could not be resolved using identical analytical protocols. Parameter estimates at 25 °C and 4°C were not different for either SHR or WKY. The number of receptors for SHR (Bmax ~ 100 fmol/105 cells) was lower than the total number of receptors for WKY (high plus low affinity ~ 430 fmol/105 cells). The intermediary KD value (~1.0 nmol) for ANP binding in SHR suggests an ANPreceptor interconversion from high affinity to low affinity in smooth muscle cells from SHR. Competition-binding experiments also revealed a decreased affinity for ANP in SHR-derived smooth muscle cells. The cyclic GMP response (intracellular accumulation and extracellular levels) was decreased in SHR smooth muscle cells compared to WKY, although this difference was evident only after prolonged (one hour) stimulation with ANP. Our data indicate a reduced sustained vascular responsiveness to ANP in hypertension. Am J Hypertens 1989; 2:32-3

m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin

Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin

The BioValley Life Sciences Week, Where Biotech and MedTech Met

For the third time the BioValley Life Sciences Week took place from October 13 to 22, 2004 in the French, German, and Swiss centers of the BioValley Life Sciences Network. Events included a 'Science et Cité' evening in Lörrach about new concepts in cancer management, the Business Platform in Freiburg where Biotech met Pharma, the 'Fête de la Science' in Strasbourg highlighting the challenges for XXIst century research, the BioValley Annual Conference in Colmar where the BioValley profile was discussed, the University Day in Strasbourg presenting the European Pharmacopoeia and looking at Drug Discovery 2004 and a sequence of events in Basel which were attended by more than 1500 persons. Events in Basel included the Science Day on systems biology and nanosciences, the Connect Day which was devoted to Partnering and Financing, the Medtech Day where this less well known but very important industry showed its cutting edge technologies, and finally the BioValley College Day attracting several hundred students from the neighboring high schools of the three countries. The BioValley Life Sciences Week has established itself firmly in the calendar of the region and will be organized again in the fall of 2005

Financing, Incubating, Coaching, and the Cluster Effect

More innovation financing, incubating and coaching would be helpful for European biotechnology. Venture capital is available for all stages of biotech company development, providing companies are innovative and of high quality. Several venture funds are active in the BioValley. To compensate for the shortcomings of management experience, a low-cost portfolio of integrated services could be provided by seasoned managers but the system has to be created, managed, and paid for by the small companies. Such shortcomings facing young companies can be overcome by seed financing, incubating and coaching, and providing a dynamic regional biotech/life sciences development organization leading to a cluster effect. This allows much better use of available assets including sparse financial means

Depth-dependant Fractionation of Light Solar Wind Noble Gases in a Genesis Target

We analyzed light noble gases in a bulk metallic glass (BMG) that was exposed to solar wind (SW) irradiation on Genesis for its total exposure time and all SW regimes [1]. The BMG was especially designed to look for a putative solar energetic particle (SEP) component, reported to be present in lunar soils [2], by using the closed system stepwise etching (CSSE) technique. Here we present the depth distribution of He and Ne isotopes and discuss different processes leading to the observed fractionation patterns. Moreover, this will be compared with measurements of Ar isotopes that are actually in progress